Liposomes are well known in the therapeutic or diagnostic field as suitable carriers for active agents, such as therapeutic and/or diagnostic compounds. Various liposome-based compositions containing active agents have been proposed, particularly for those agents showing a reduced half-life in the blood stream. For instance, U.S. Pat. No. 6,143,321 discloses liposomes containing a micellar preparation entrapped in the interior space thereof, said micellar preparation comprising an active agent aggregated with a lipid surfactant to form a micelle.
Diagnostic imaging employing agents capable of enhancing the images obtainable with different imaging techniques (known as “contrast agents” or “image enhancing agents”) has also become a rather widely adopted practice.
For instance, iodinated products, such as Iopamidol® or Iomeprol® (Bracco Imaging S.p.A.), are widely employed in X-ray contrast analysis, in particular computer tomography (Cr) X-ray, whilst compounds containing paramagnetic ions such as ProHance® or MultiHance® (Bracco Imaging), are widely employed in MRI analysis.
Among the various properties of an image enhancing agent, some of those which are probably more desirable are a high image enhancing capability and a sufficiently long residence time thereof in the relevant system, tissue or organ to be visualized. Many efforts have thus been dedicated in the past to improve these two properties of contrast agents.
For instance, U.S. Pat. No. 6,217,849 discloses aqueous suspension of liposomes for x-ray or NMR imaging having improved capability of remaining in the blood circulation.
U.S. Pat. No. 5,387,410 suggests using a liposome to carry a paramagnetic ion chelate within or outside the external surface thereof, in order to obtain an enhanced NMR imaging of a selected organ.
U.S. Pat. No. 5,833,948 teaches to incorporate paramagnetic ion chelates into micellar structures comprising a non-ionic surfactant, to improve the blood-pool properties thereof.
U.S. Pat. No. 5,756,069 relates to the problem of increasing the concentration of a MRI responsive agent on carriers, such as liposomes, to provide a useful image. Polychelating compounds are disclosed which are capable of binding a plurality of paramagnetic ions and comprising a lipid-soluble anchor to bound the compound to a liposome or a micelle.
Furthermore, image enhancing compounds can also be used in combination with targeting compounds (which allow to link the image enhancing compound to a specific target site—e.g. a tissue, an organ or specific cells—in order to selectively enhance the imaging thereof) and/or with therapeutic agents (e.g. which can be released at a corresponding site, tissue or organ upon visualization thereof).